Fibroblasts cultured from a patient with the syndrome of leprechaunism (characterized by physical abnormalities, intrauterine growth retardation, and clinical insulin resistance) exhibit abnormalities of insulin receptors, receptors for insulin-like growth factors (IGFs), and impaired stimulation of glucose incorporation by these hormones using these receptors. In our studies of the insulin-like growth factor (somatomedin) multiplication stimulating activity (MSA), a polypeptide synthesized by a cloned line of rat liver cells (BRL 3A), progress has been made in the following areas: (i) purification of MSA to homogeneity and determination of its amino acid composition; (ii) development of a radioimmunoassay for MSA; (iii) demonstration that receptors for the insulin-like growth factors are heterogeneous; (iv) demonstration of two structural subtypes of IGF receptors using chemical crosslinking techniques; (v) demonstration that insulin and MSA utilize insulin and MSA receptors, respectively, to mediate the same biological responses in rat hepatoma cells, chondrosarcoma cells, and human fibroblasts; (vi) demonstration that MSA is the major somatomedin in fetal rat serum, and that MSA levels fall shortly after birth; (vii) characterization of growth hormone-dependent binding proteins for somatomedins in rat and human serum.